Rachel Nygaard

E-mail: nyga0078@umn.edu

Thesis advisor: Leslie Schiff

Year entered: 2006

Degree received:
B.S., Biology, Central Missouri State University, Warrensburg, MO 2001

Honors and Awards:

• DOVE Fellowship 2006
  

Thesis research:
Mammalian reoviruses naturally infect hosts via the enteric and/or respiratory routes. Productive infection depends upon host-expressed proteases to remove the outer capsid protein sigma-3 and expose the underlying membrane penetration protein mu-1, creating an infectious subvirion particle (ISVP). Although secreted pancreatic serine proteases are believed to mediate proteolysis in the enteric tract, the proteases necessary for respiratory tract infection remain unknown. With the goal of identifying these proteases, we are using a well-established mouse model of reovirus-induced acute respiratory distress syndrome. To determine if the requirement for proteolysis limits infection in the respiratory tract, we infected mice intranasally with virions or ISVPs and analyzed viral growth and spread. We found that ISVPs replicated with faster kinetics than virions in the lungs, but that virions and ISVPs reached equivalent yields. These results suggest that proteolysis is a rate-limiting step during respiratory infection. Infections initiated with ISVPs also resulted in more severe gross pathology and more rapid spread to tissues outside of the respiratory tract. The enhanced spread could reflect a broader host range of ISVPs because they do not require host proteases for infectivity. Alternatively, ISVPs may have increased access to M cells in the nasal associated lymphoid tissue because sigma-3 removal results in extension of sigma-1, the cell attachment protein. We are currently examining the relative importance of specific extracellular and intracellular proteases in respiratory reovirus infection, and using immunohistochemistry to identify the types of cells infected after intranasal infection.